The major long-term objective of this program is a better understanding of the precataractous changes in elemental composition which occur at the cellular level in highly localized regions of the lens. This includes localized changes in the electrolytes, Na, K, and Cl, which may precede the onset of hydration and opacification. An understanding of how such changes are related to the development of cataracts, and how this information may be useful in development of procedures to prevent or delay the onset of cataractogenesis is the long term goal. The application of energy dispersive x-ray analysis in conjunction with scanning electron microscopy to the quantitative elemental analysis of individual cells and groups of cells in the normal and cataractous lens is the primary methodology for achieving these goals. The diffusible elements, notably Na, K, and Cl, will be studied in rapidly-frozen lens tissue. Cryosections containing superficial fibers, epithelium, and capsule in their normal structural relationship as well as other regions of the normal and cataractous lens, will be used along with internal standards. Also, lenses which have been rapidly-frozen along with internal standards, fractured and dried, will provide bulk specimens for elemental profiles of the whole lens, or for small defined regions of the normal or cataractous lens identified by CCRG photography. The major effort will be directed toward quantitative elemental analysis in lenses at various stages leading up to and including the early stages of opacification in the rat galactose cataract, the Nakano mouse cataract and the ouabain-induced cataract in the cultured rabbit lens, and at various stages during the reversal of the galactose cataract. Human cataracts, particularly supranuclear, will be analyzed for the concentrations of electrolytes in the opacities as compared to the transparent regions.